Post-operative complications after colorectal cancer surgery increased with higher BMI.

INTRODUCTION: Because of conflicting evidence regarding overweight and post-operative complications, this study focused on post-operative complications and death within 30 and 90 days after curatively intended surgery for colorectal cancer and its association with BMI. METHODS: The study included all patients who had potentially curative surgery for colon or rectum cancer in Denmark from 2014 through 2018. The primary endpoint was post-operative complications within 30 days of surgery and secondary endpoints were 30- and 90-day mortality. All clinically relevant confounders were included in a multivariate analysis. RESULTS: The cohort included 14,004 patients. In the multivariate logistic regression analysis, adjusting for relevant confounders, we found the odds ratio of having a surgical complication or having both a surgical and medical complication at the same time to be rising with increasing weight class. The multivariate analysis showed the odds ratio for both 30- and 90-day mortality to be higher for underweight patients and for obesity class III patients, but the rest of the patients had no significant differences in relative risk compared with normal-weight patients. CONCLUSION: Based on our results, the risk of post-operative complications rises with increasing weight, whereas post-operative morbidity is increased only in the underweight and morbidly obese patients. FUNDING: none. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency (REG-008-2020).

Impact of screening on short-term mortality and morbidity following treatment for colorectal cancer.

BACKGROUND AND OBJECTIVE: The aim of this study was to describe short-term changes in morbidity and mortality associated with the implementation of screening for colorectal cancer in Denmark. METHODS: Prospective cohort study with inclusion of all patients aged 50-75 years treated for colorectal cancer between 1 March 2014 and 31 December 2015 in Denmark. Adjusted hazard ratios were calculated for 30 and 90 days mortality using Cox Regression. We made two adjusted models-a "basic" adjusted for screening status, sex, age, smoking, alcohol consumption, and cancer type and an "advanced" that also included body mass index and American society of Anesthesiologists score in analyses. Relative risks were calculated for postoperative surgical and medical complications. RESULTS: In total, 5348 patients were included. In the "basic model," adjusted risk of 30 and 90 days total mortality was reduced in the screen-detected group (p < 0.01, HR = 0.43, CI = 0.24-0.76) and (p < 0.01, HR = 0.45, CI = 0.30-0.69). In the "advanced model," only 90 days total mortality was significantly reduced in the screen-detected group (p = 0.01, HR 0.59, CI = 0.39-0.90). No significant changes were found with regard to surgical and medical complications, respectively, (p = 0.05 (CI = 0.76-1.00) and p = 0.47(CI = 0.74-1.15)). CONCLUSIONS: This nationwide study showed that screening for colorectal cancer was associated with a lower 90 days total mortality although no significant improvements were seen with regard to morbidity.

The optimal cut-off value in fit-based colorectal cancer screening: An observational study.

BACKGROUND: Colorectal cancer (CRC) screening programs using fecal immunochemical test (FIT) have to choose a cut-off value to decide which citizens to recall for colonoscopy. The evidence on the optimal cut-off value is sparse and based on studies with a low number of cancer cases. METHODS: This observational study used data from the Danish Colorectal Cancer Screening Database. Sensitivity and specificity were estimated for various cut-off values based on a large number of cancers. Traditionally optimal cut-off values are found by weighting sensitivity and specificity equally. As this might result in too many unnecessary colonoscopies we also provide optimal cut-off values for different weighting of sensitivity and specificity/number of needed colonoscopies to detect one cancer. RESULTS: Weighting sensitivity and specificity equally gives an optimal cut-off value of 45 ng Hb/ml. This, however, means making 24 colonoscopies to detect one cancer. Weighting sensitivity lower and for example, aiming at making about 16 colonoscopies to detect one cancer, gives an optimal cut-off value of 125 ng Hb/ml. CONCLUSIONS: The optimal cut-off value in an FIT population-based screening program is 45 ng Hb/ml, when as traditionally sensitivity and specificity are weighted equally. If, however, 24 colonoscopies needed to detect one cancer is too huge a burden on the health care system and the participants, 80, 125, 175, and 350 ng Hb/ml are optimal cut-off values when only 19/16/14/10 colonoscopies are accepted to find one cancer.

Identification of Risk Factors Associated With Stage III Disease in Nonmetastatic Colon Cancer: Results From a Prospective National Cohort Study.

PURPOSE: This study aimed to identify possible patient- and tumor-related factors associated with risk of TNM stage III disease in nonmetastatic colon cancer. METHODS: The associations between stage III disease and age, sex, lymph node yield, pathological tumor (pT) stage, tumor subsite, type of surgery, and priority of surgery were assessed in a nationwide cohort of 13,766 patients treated with curative resection of colon cancer. Each level of age, lymph node yield, and pT stage was compared to the preceding level. RESULTS: Age, lymph node yield, pT stage, tumor subsite, and priority of surgery were associated with stage III disease. Odds ratios (95% confidence interval [CI]) were as follows: age < 65/65-75 years: 1.28 (95% CI, 1.15-1.43) and 65-75/ > 75 years: 1.22 (95% CI, 1.13-1.32); lymph node yield 0-5/6-11: 0.60 (95% CI, 0.50-0.72), lymph node yield 6-11/12-17: 0.84 (95% CI, 0.76-0.93), and lymph node yield 12-17/ ≥ 18: 0.97 (95% CI, 0.89-1.05); pT1/pT2: 0.74 (95% CI, 0.57-0.95), pT2/pT3: 0.35 (95% CI, 0.30-0.40), and pT3/pT4: 0.49 (95% CI, 0.47-0.54). Only tumors of the transverse colon were independently associated with lower risk of stage III disease than tumors in the sigmoid colon (sigmoid colon: 1, transverse colon: 0.84 [95% CI, 0.73-0.96]; elective surgery: 1, acute surgery: 1.43 [95% CI, 1.29-1.60]). CONCLUSION: In this study, stage III disease in colon cancer was significantly associated with age, lymph node yield, pT stage, tumor subsite, and priority of surgery but was not associated with right-sided location compared with stage I and II cancers.

Lymph node yield and tumour subsite are associated with survival in stage I-III colon cancer: results from a national cohort study.

BACKGROUND: It has been suggested that apart from tumour and nodal status, a range of patient-related and histopathological factors including lymph node yield and tumour location seems to have prognostic implications in stage I-III colon cancer. We analysed the prognostic implication of lymph node yield and tumour subsite in stage I-III colon cancer. METHODS: Data on patients with stage I to III adenocarcinoma of the colon and treated by curative resection in the period from 2003 to 2011 were extracted from the Danish Colorectal Cancer Group database, merged with information from the Danish National Patient Register and analysed. RESULTS: A total of 13,766 patients were included in the analysis. The 5-year overall survival ranged from 59.3% (95% CI 55.7-62.9%) (lymph node yield 0-5) to 74.0% (95% CI 71.8-76.2%) (lymph node yield ≥ 18) for patients with stage I-II disease (p < 0.0001) and from 36.4% (95% CI 29.8-43.0%) (lymph node yield 0-5) to 59.4% (95% CI 56.6-62.2%) (lymph node yield ≥ 18) for patients with stage III disease (p < 0.0001). The 5-year overall survival for tumour side left/right was 59.3% (95% CI 57.9-60.7%)/64.8% (CI 63.4-66.2%) (p < 0.0001). In the seven colonic tumour subsites, the 5-year overall survival ranged from 56.6% (95% CI 51.8-61.4%) at splenic flexure to 65.8% (95% CI 64.5-67.2%) in the sigmoid colon (p < 0.0001). In a cox regression analysis, lymph node yield and tumour side right/left were found to be prognostic factors. Tumours at the hepatic and splenic flexures had an adverse prognostic outcome. CONCLUSION: For stage I-III colon cancer, a lymph node yield beyond the recommended 12 lymph nodes was associated with improved survival. Both subsite in the right colon, as well as subsite in the left colon, turned out with adverse prognostic outcome questioning a simple classification into right-sided and left-sided colon cancer.

Three years of colorectal cancer screening in Denmark.

BACKGROUND: The Danish National Colorectal Cancer Screening Programme was implemented in March 2014 and is offered free of charge to all residents aged 50-74 years. The aim of this study is to compare performance indicators from the Danish National Colorectal Cancer Screening Programme to the recommendations from European Guidelines in order to assure the quality of the programme and to provide findings relevant to other population-based colorectal cancer screening programmes. METHODS: Based on data from the Danish Colorectal Cancer Screening Database, we evaluated all performance indicators for which the European Guidelines provided acceptable level, desirable level or the level from first screening rounds in population-based studies using FIT. RESULTS: All performance indicators were above the acceptable level and/or in line with the level from the first screening round in population-based studies using FIT. Whenever the European Guidelines provided a desirable level for a performance indicator, the Danish National Colorectal Cancer Screening Programme was close to or above this desirable level. CONCLUSIONS: Compared to the European Guidelines, all performance indicators were above the acceptable level and close to the desirable level. Based on these findings, the implementation of the National Danish Colorectal Cancer Screening Programme is considered a success and the programme is hopefully in the process of reducing colorectal cancer morbidity and mortality in Denmark. This study provides relevant information for comparisons to other population-based public service colorectal cancer screening programmes as well as for future revisions of guidelines.

A model predicting operative mortality in the UK has only limited value in Denmark.

PURPOSE: Postoperative mortality from colorectal cancer varies between surgical departments. Several models have been developed to predict the operative risk. This study aims to investigate whether the original and the revised Association of Coloproctology of Great Britain and Ireland (ACPGBI) model can predict 30-day mortality after colorectal cancer surgery in Denmark. METHODS: Data were collected from the Danish Colorectal Cancer Group database which has > 95% completeness. All patients operated on from January 2007 to December 2013 were included. The individual estimated operative risk was calculated with the original and revised ACPGBI models. Discrimination and calibration were evaluated with a Receiver Operating Characteristic (ROC) curve analysis and a Hosmer-Lemeshow test, respectively. RESULTS: In total, 22,807 patients underwent open or laparoscopic colorectal cancer surgery. After excluding 1437 patients because of missing data, 21,370 patients were left for the analyses. The observed 30-day mortality was 5.0%. The original and revised ACPGBI models estimated an operative risk of 7.0 and 4.0%, respectively, with a significant difference in observed and estimated mortality in both models. However, in patients with an estimated risk of at least 26%, i.e., high-risk, good calibration was found with the original ACPGBI model. Discrimination was good with an AUC of 0.83 (95% CI 0.82-0.84) in both models. CONCLUSION: The original and revised ACPGBI models are not suitable prediction models for postoperative mortality in the Danish colorectal cancer population. However, the original model might be applicable in predicting mortality in high-risk patients.

A high lymph node yield in colon cancer is associated with age, tumour stage, tumour sub-site and priority of surgery. Results from a prospective national cohort study.

AIM: To determine the relation between patient-related and histopathological factors, as well as the influence of national programs for diagnosing and treatment of colon cancer and a lymph node yield (LNY) ≥ 12. METHOD: An analysis was carried out of the LNY in a nationwide Danish cohort treated by curative resection of stage I-III colon cancer in the period 2003-2011. The association between a LNY ≥ 12 and age, sex, body mass index, open vs. laparoscopic surgery, acute vs. elective surgery, pT stage, tumour sub-site and year of diagnosis was analysed. RESULTS: A total of 13,766 patients were eligible for the analysis. In total, 71.4 % of the patients had a LNY ≥ 12. In multivariate analysis, age, pT stage, tumour sub-site and priority of surgery were independently associated with the probability of a LNY ≥ 12. Odds ratios (ORs) were as follows: age <65 1, 65-75 0.685 (confidence interval (CI) 0.586-0.800), >75 0.517 (CI 0.439-0.609); T1 1, T2 2.750 (CI 2.168-3.487), T3 6.016 (CI 4.879-7.418), T4 6.317 (CI 4.950-8.063); right colon 1, left colon 0.568 (0.511-0.633); elective surgery 1, acute surgery 0.748 (CI 0.625-0.894). Moreover, year of diagnosis was associated with the probability of a LNY ≥ 12: OR 1.480 (CI 1.445-1.516) for each increasing year in the study period. CONCLUSION: A LNY ≥ 12 is significantly associated with age, pT stage, tumour sub-site and priority of surgery. A significant increase in the LNY over the period of the study was observed, probably reflecting the effect of national programmes initiated by the Danish Colorectal Cancer Group.

Increased Lymph Node Yield Is Associated With Improved Survival in Rectal Cancer Irrespective of Neoadjuvant Treatment: Results From a National Cohort Study.

BACKGROUND: It has been proposed that the lymph node yield achieved during rectal cancer resection is associated with survival. It is debated whether a high lymph node yield improves survival, per se, or whether it does so by diminishing the International Union Against Cancer stage drifting effect. OBJECTIVE: The purpose of this study was to evaluate the prognostic implications of the lymph node yield in curative resected rectal cancer. DESIGN: This study was based on data from a prospectively maintained colorectal cancer database. SETTINGS: This was a national cohort study. PATIENTS: All 6793 patients in Denmark who were diagnosed with International Union Against Cancer stage I to III adenocarcinoma of the rectum and so treated in the period from 2003 to 2011 were included in the analysis. MAIN OUTCOME MEASURES: The primary outcome measure was overall survival. RESULTS: The observed percentages of patients with International Union Against Cancer stage III disease with a lymph node yield less than 12 or 12 or more were 28.1 % and 40.7% (p < 0.0001) in the non-neoadjuvant treatment group and 26.9% and 38.3% (p < 0.0001) in the neoadjuvant treatment group. The 5-year overall survival rates for patients with a lymph node yield <12 or 12 or more were 73.1% and 80.6% in International Union Against Cancer stages I to II (p < 0.0001) and 57.4% and 53.3% in stage III (p < 0.142) in the neoadjuvant treatment group and 70.4% and 79.2% in stages I to II (p < 0.0001) and 46.6% and 59.1% in International Union Against Cancer stage III (p < 0.0001) in the non-neoadjuvant treatment group. In multivariate analysis, the lymph node yield turned out to be an independent prognostic factor, irrespective of neoadjuvant treatment. LIMITATIONS: It is not possible in an observational study to tell whether the findings are associations rather than causal relationships. CONCLUSIONS: Increased lymph node yield was associated with better overall survival in rectal cancer, irrespective of neoadjuvant treatment. Stage migration was observed.

A minimum yield of twelve lymph nodes in rectal cancer remains valid in the era of neo-adjuvant treatment : results from a national cohort study.

PURPOSE: The purpose of the study was to examine if a minimum of 12 lymph nodes (LNs) is still valid in rectal cancer after neo-adjuvant treatment. METHODS: An analysis was carried out in a nationwide Danish cohort of 6793 patients, treated by curative resection of stage I-III rectal cancer during the period 2003-2011. The cohort was divided into two groups according to whether neo-adjuvant treatment had been given. The groups were analysed separately and were further analysed according to four lymph node yield (LNY) groups 0-5, 6-11, 12-17 and ≥18. RESULTS: Two thousand one hundred twenty-three patients (31.0 %) received neo-adjuvant treatment. A median LNY of 10 and 15 (p < 0.0001) and rates of node-positive (N-positive) disease of 31.6 and 36.7 % (p < 0.001) were observed with and without (+/-) neo-adjuvant treatment, respectively. The rate of N-positive disease according to tumour stage ranged from 4.8 %/11.4 % (ypT0/pT1) to 42.1 %/64.1 % (ypT4/pT4). The rate of N-positive disease according to LNY ranged from 19.5 %/16.8 % (0-5 LNs) to 42.6 %/37.9 % (≥18 LNs) (-/+neo-adjuvant treatment). In a logistic regression analysis, a significant association was found between N-positive disease and pT/ypT stage as well as between N-positive disease and LNY. CONCLUSIONS: A significantly smaller ratio of N-positive disease was observed in the group of patients who had received neo-adjuvant treatment. The ratio of N-positive disease increased significantly with more advanced tumour stage and increasing LNY irrespective of neo-adjuvant treatment. A minimum of 12 LNs is needed to ensure N-negative disease, irrespective of neo-adjuvant treatment.

The majority of surgical departments adhere to national Danish guidelines for surveillance after colorectal cancer surgery.

INTRODUCTION: In 2003 the use of post-operative surveillance (POS) after surgery for colorectal cancer (CRC) in Denmark was studied. Diversity in the choice and frequency of surveillance modalities was found. Subsequently, the Danish Colorectal Cancer Group (DCCG) has published guidelines for POS. In the same period, the number of departments performing CRC surgery has been reduced by 50% nationally. The aim of the present study was to describe the POS after CRC in Denmark following a reduction in the number of departments performing operations for CRC and the DCCG's publication of national recommendations for POS programmes. MATERIAL AND METHODS: Questionnaires were sent to all 19 departments that performed operations for CRC. Questions concerned the diagnostic modalities used for detecting recurrences and metachrone cancers. RESULTS: All departments returned their questionnaires. All departments had a formal POS programme. The recommendations given by the DCCG were met by 17 departments (89%) with regard to liver metastases, by 16 departments (84%) with regard to lung metastases and by 16 departments (84%) with regard to metachrone cancers. CONCLUSION: As opposed to what was observed in 2003, all departments offered a POS programme after CRC surgery in 2012. Almost all departments met the DCCG recommendations, probably owing to the centralization of CRC surgery and the DCCG's introduction of national guidelines. Hopefully, this will contribute to a better survival for CRC patients in the future, although more research is needed to establish optimal post-operative surveillance. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Increased levels of C-reactive protein and leukocyte count are poor predictors of anastomotic leakage following laparoscopic colorectal resection.

INTRODUCTION: Laparoscopic procedure and fast-track regimen with short post-operative hospital stay are gaining ground in colorectal surgery. The aim of the present study was to determine whether the levels of C-reactive protein (CRP) and white blood cell counts (WBC) have a role as early predictors of post-operative septic complications including anastomotic leakage in patients operated laparoscopically in a fast-track regimen. MATERIAL AND METHODS: This was a retrospective analysis of 129 patients who underwent laparoscopic colorectal surgery in a fast-track regimen during a one-year period. The levels of CRP and WBC were measured daily until discharge. The diagnostic accuracy was evaluated using the receiver-operating characteristics methodology. RESULTS: The median post-operative hospital stay was three days. Septic complications occurred in 32% of cases. Post-operative CRP level was significantly higher in patients with septic complications than in patients without complications, but similar in patients with anastomotic leakage and patients with other septic complications. The best cut-off value for CRP level as a predictor of septic complications was observed on post-operative day (POD) 3, where CRP concentration > 200 mg/l had a sensitivity of 68% and a specificity of 74%. WBC measurements showed the best cut-off value on POD 2, where WBC > 12 × 10(9) had a sensitivity of 90% and a specificity of 62%. CONCLUSION: The insufficient diagnostic accuracy of the levels of CRP and WBC made them weak diagnostic markers in prediction of post-operative septic complications, including anastomotic leakage, in the first three post-operative days after laparoscopic colorectal surgery.